In patients of renal function disorder, disorder of phosphorus excretion in the urine is observed, and in the early stages of renal failure a renal compensation mechanism works to keep phosphorus homeostasis, temporarily showing increase of phosphorus excretion by inhibiting a phosphorus re-absorption due to increase of PTH (parathyroid hormone). However, it becomes impossible to keep the homeostasis due to aggravation of a renal lesion and lowering of a renal function. As a result, hyperphosphatemia due to reduction of phosphorus excretion and a remarkable increase of PTH occurs. The accumulated phosphorus induces, as direct actions, lowering of blood calcium, acceleration of PTH production/secretion, ectopic calcification and renal osteodystrophy due to suppression of vitamin D activation. Also, as indirect actions via high PTH level, central and peripheral nerve disorders, myocardial disorders, hyperlipemia, saccharometabolism disorders, muscle disorders, growth retardation, cardiac conduction disorders, alveolar diffusion disorders, arteriosclerosis and immunodeficiency are shown. Further, as to phosphorus the aspect as a uremic substance and its direct or indirect involvement for complications of renal failure are known (Jin to Toseki, 37, 2: 321, 1994).
Even if treatment is changed to a dialysis therapy due to renal failure, the above disease conditions and complications continue unless the phosphorus homeostasis is maintained. Consequently, treatment of hyperphosphatemia is essential for dialysis patients of renal failure or patients before dialysis. At present, in the treatment of hyperphosphatemia a diet therapy or an oral phosphorus adsorbent are used. In the diet therapy low protein diet is used, though the intake for long period is difficult, and protein intake of a certain degree is unavoidable, wherefore the effect to lower phosphorus in blood cannot necessarily be expected.
As oral phosphorus adsorbents, mainly three types in the following are currently used.
1) Aluminum preparation (aluminum hydroxide)
2) Calcium preparation (calcium carbonate, calcium acetate)
3) Magnesium preparation (magnesium carbonate)
In 1) side effects of aluminum encephlopathy and aluminum osteopathy due to aluminum absorption are problems; in 2) the adsorbability is inferior compared with the aluminum preparation, and additionally the dose is also high, giving a problem of inducing hypercalcemia due to calcium absorption; further, in 3) there is a problem of inducing hypermagnesemia as in the calcium preparation.
Methods for using an anion exchange resin as an oral phosphorus adsorbent have been reported in recent years. In JP, A, 9-504782 (WO95/05184) an anion exchange resin in which polyallyl amine is crosslinked with epichlorohydrin is reported as a phosphoric acid adsorbent. Also, in JP, A, 8-506846, WO96/25440, it is reported that the anion exchange resin having a guanythidyl group selectively adsorbs phosphoric acid. Further, in JP, A, 9-295941, 2-methylimidazole-epichlorohydrin copolymer and cholestyramine which are bile acid adsorbents are applied as oral phosphorus adsorbents. However, all have a defect that use of a high dose is necessary because of a remarkable reduction of phosphate absorption.
As described above, in a currently carried out hyperphosphatemia treatment, bad effects are concerned in any method. Therefore, the present situation is such that a better remedy for hyperphosphatemia has not been found out up to now.
On the other hand, although it is known that a weakly basic anion exchange resin known under the trade name, for example, such as Ionac A-365 (Sybron Chemicals Co.) is used to remove hydrochloric acid in an aqueous system and a non-aqueous system, there has been no report to date in which this is used as a phosphoric acid adsorbent.